Saccharomyces cerevisiae Thi4

Steve Ealick's Research Group

Saccharomyces cerevisiae Thi4

PDB file:

2GJC; Thi4 complexed with adenosine diphospho-5-(β-ethyl)-4-methyl-thiazole-2-carboxylic acid (ADT)

Description:

In contrast to bacteria, thiamin biosynthetic studies in eukaryotes are still at an early stage. Labeling studies in Saccharomyces cerevisiae have demonstrated that the thiamin thiazole is biosynthesized from an unidentified five carbon carbohydrate.The structure of the S. cerevisiae thiazole synthase (Thi4) was solved by molecular replacement (PDB code1RP0) and reveals the nature of binding to ADT found in the enzyme active site. The identification of this product suggests that NAD is the source of the carbohydrate precursor.

The Thi4 monomer consists of ten β-strands and nine α-helices. Both the N and C terminal helices are amphipathic. ADT is shown bound to the active site.

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Thi4 exists as an octamer with two monomers in the asymmetric unit. The octameric complex may be viewed as a tetramer of dimers with many interdimeric contacts at the interface between two monomers. The outer and inner surfaces are lined with hydrophilic residues.

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ADT was bound to the Thi4 active site, which is located near the inner ring of the octameric complex. The adenosine moiety runs along the first β-strand in the fold characteristic of a dinucleotide binding site.

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References

Jurgenson CT, Chatterjee A, Begley TP and Ealick SE. Structural insights into the function of the thiamin biosynthetic enzyme Thi4 from Saccharomyces cerevisiae. Biochemistry 45:11061-11070 (2006).

Chatterjee A, Jurgenson CT, Schroeder FC, Ealick SE, and Begley TP. Thiamin Biosynthesis in Eukaryotes: Characterization of the Enzyme-Bound Product of Thiazole Synthase from Saccharomyces cerevisiae and Its Implications in Thiazole Biosynthesis. J. Am. Chem. Soc. 128:7158-7159 (2006).